Mice deficient in antigen receptor rearranging activity due to a disruption of the RAG-2 gene have no B or T cells, but all other components of the immune system (macrophages, NK cells) are intact. When rearranged antigen receptor genes are introduced by breeding into the RAG-2 deficient background, discrete populations of lymphoid cells develop which reflect the expression of the introduced gene. When all necessary components of the B cell antigen receptor are expressed, a developmentally and functionally synchronized population of monoclonal B cells develops in the absence of T cells. This murine model will allow the candidate to undertake the study and detailed characterization of primary cells which are intermediates in this developmental process, and to elucidate the factors involved in peripheral B cell activation and somatic hypermutation of the B cell receptor during the humoral immune response. The research has potentially important implications for the understanding of hematologic and immunodeficiency disease, the genesis of lymphoid malignancies, and biologic therapies such as bone marrow transplantation and gene therapy.